- Fluorouracil (5-FU) and Capecitabine, an oral prodrug of 5-FU, are fluoropyrimidine chemotherapy agents used in the treatment of primary (early) and secondary (metastatic) cancers at tertiary centres across the region. Colorectal, breast, oesophagogastric, heapato-pancreato-biliary and head and neck cancers are exemplars of cancers where fluoropyrimidine chemotherapy is a backbone of therapy.
- 5-FU and capecitabine are catabolised by the dihydropyrimadine deyhydrogenase (DPD) enzyme in the liver. The DPD enzyme, encoded by the DPYD gene, deactivates more than 80% of standard doses of 5-FU and capecitabine. Approximately 3–5% of the European population have a partial DPD enzyme deficiency whereas complete DPD enzyme deficiency is rare, with a prevalence of 0.01–0.1%. Patients with complete DPD deficiency are unable to catabolise (breakdown) 5-FU, leading to rapid onset, life-threatening or fatal chemotherapy toxicity. In the last 2 years there have been 2 patient deaths due to undetected DPD deficiency associated toxicity at The Christie Foundation Trust. Patients with a partial DPD deficiency typically experience increased toxicity, hospital admissions, treatment deferrals and dose reductions.
- In screening for the DPYD genotype we are able to detect genetic variants leading to DPD enzyme deficiency. Placing this screening prior to fluoropyrimidine treatment, as a new standard of care, will prevent significant or life threatening toxicity within this treatment.
- 5ml EDTA sent to Liverpool women’s hospital directly or using existing transport via mft.